| Title: |
Accelarated immune ageing is associated with COVID-19 disease severity. |
| Authors: |
Lord, Janet M; Veenith, Tonny; Sullivan, Jack; Sharma-Oates, Archana; Richter, Alex G; Greening, Neil J; McAuley, Hamish JC; Evans, Rachael A; Moss, Paul; Moore, Shona C; Turtle, Lance; Gautam, Nandan; Gilani, Ahmed; Bajaj, Manan; Wain, Louise V; Brightling, Christopher; Raman, Betty; Marks, Michael; Singapuri, Amisha; Elneima, Omer; Openshaw, Peter JM; Duggal, Niharika A; PHOSP-COVID Study collaborative group; ISARIC4C investigators |
| Publisher Information: |
Springer Nature; //doi.org/10.1186/s12979-023-00406-z |
| Publication Year: |
2024 |
| Collection: |
Apollo - University of Cambridge Repository |
| Subject Terms: |
32 Biomedical and Clinical Sciences; 3204 Immunology; Clinical Research; Coronaviruses; Infectious Diseases; Lung; Aging; Immunotherapy; Emerging Infectious Diseases; Coronaviruses Disparities and At-Risk Populations; 2.1 Biological and endogenous factors; Infection; 3 Good Health and Well Being |
| Description: |
BACKGROUND: The striking increase in COVID-19 severity in older adults provides a clear example of immunesenescence, the age-related remodelling of the immune system. To better characterise the association between convalescent immunesenescence and acute disease severity, we determined the immune phenotype of COVID-19 survivors and non-infected controls. RESULTS: We performed detailed immune phenotyping of peripheral blood mononuclear cells isolated from 103 COVID-19 survivors 3-5 months post recovery who were classified as having had severe (n = 56; age 53.12 ± 11.30 years), moderate (n = 32; age 52.28 ± 11.43 years) or mild (n = 15; age 49.67 ± 7.30 years) disease and compared with age and sex-matched healthy adults (n = 59; age 50.49 ± 10.68 years). We assessed a broad range of immune cell phenotypes to generate a composite score, IMM-AGE, to determine the degree of immune senescence. We found increased immunesenescence features in severe COVID-19 survivors compared to controls including: a reduced frequency and number of naïve CD4 and CD8 T cells (p < 0.0001); increased frequency of EMRA CD4 (p < 0.003) and CD8 T cells (p < 0.001); a higher frequency (p < 0.0001) and absolute numbers (p < 0.001) of CD28-ve CD57+ve senescent CD4 and CD8 T cells; higher frequency (p < 0.003) and absolute numbers (p < 0.02) of PD-1 expressing exhausted CD8 T cells; a two-fold increase in Th17 polarisation (p < 0.0001); higher frequency of memory B cells (p < 0.001) and increased frequency (p < 0.0001) and numbers (p < 0.001) of CD57+ve senescent NK cells. As a result, the IMM-AGE score was significantly higher in severe COVID-19 survivors than in controls (p < 0.001). Few differences were seen for those with moderate disease and none for mild disease. Regression analysis revealed the only pre-existing variable influencing the IMM-AGE score was South Asian ethnicity ([Formula: see text] = 0.174, p = 0.043), with a major influence being disease severity ([Formula: see text] = 0.188, p = 0.01). ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
https://www.repository.cam.ac.uk/handle/1810/365428 |
| Availability: |
https://www.repository.cam.ac.uk/handle/1810/365428 |
| Rights: |
Attribution 4.0 International ; https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.5843FE97 |
| Database: |
BASE |